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Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia.

Authors :
Li Yu
Chunhui Liu
Vandeusen, Jeff
Becknell, Brian
Zunyan Dai
Yue-Zhong Wu
Raval, Aparna
Te-Hui Liu
Wei Ding
Charlene Mao
Shujun Liu
Smith, Laura T
Lee, Stephen
Rassenti, Laura
Marcucci, Guido
Byrd, John
Caligiuri, Michael A
Plass, Christoph
Source :
Nature Genetics; Mar2005, Vol. 37 Issue 3, p265-274, 10p
Publication Year :
2005

Abstract

DNA methylation is associated with malignant transformation, but limitations imposed by genetic variability, tumor heterogeneity, availability of paired normal tissues and methodologies for global assessment of DNA methylation have limited progress in understanding the extent of epigenetic events in the initiation and progression of human cancer and in identifying genes that undergo methylation during cancer. We developed a mouse model of T/natural killer acute lymphoblastic leukemia that is always preceded by polyclonal lymphocyte expansion to determine how aberrant promoter DNA methylation and consequent gene silencing might be contributing to leukemic transformation. We used restriction landmark genomic scanning with this mouse model of preleukemia reproducibly progressing to leukemia to show that specific genomic methylation is associated with only the leukemic phase and is not random. We also identified Idb4 as a putative tumor-suppressor gene that is methylated in most mouse and human leukemias but in only a minority of other human cancers. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10614036
Volume :
37
Issue :
3
Database :
Complementary Index
Journal :
Nature Genetics
Publication Type :
Academic Journal
Accession number :
16244852
Full Text :
https://doi.org/10.1038/ng1521